This Independent Scientist Award (K02) renewal application describes career development activities and a program of research focusing on links between sleep, arousal, and affect regulation. The conceptual framework emphasizes a developmental perspective and clinically relevant hypotheses regarding pathways to adolescent depression. This application outlines four new or modified aims to the previous work: 1) To sharpen the developmental focus to the period of early adolescence/onset of puberty as a time of brain maturation with particular relevance to the development of affect regulation (and affective disorders). 2) To strengthen the cognitive-neuroscience approach to understanding affect regulation and depression in adolescence (including methodological and conceptual advances in the use of neuroimaging studies). 3) To expand the clinical outcomes of interest to include adolescent alcohol and nicotine use. 4) To use experience-sampling methodologies to obtain ecologically valid assessments (EMA) of mood, behavior, and sleep patterns in adolescents' home environments. The research plans to carry out these aims include ongoing and planned studies in pert-pubertal subjects to investigate early adolescent brain maturation and functional brain changes associated with depression. The research also includes longitudinal clinical follow-up studies of subjects (samples of normal controls, high-risk, anxious, and depressed children) who previously underwent comprehensive psychobiologic and maturational assessments. These samples are being followed through late adolescence and into early adulthood to examine developmental pathways to depression, nicotine, and alcohol use. This research (along with the linked career development activities) will lead to a better understanding of brain maturation in early adolescence and the development of affect regulation. The long-term goals are to inform early interventions to help prevent the development of adolescent-onset affective disorders and substance dependence.